In order to reduce the high cost of HDC vaccine, effort will be made to simplify vaccine production and eventually to replace human diploid cells by another acceptable but less costly cell substrate. The study of in vitro production of anti rabies antibodies (hybridoma cell cultures) to be used for prophylaxis of rabies in humans will be given first priority. We will continue investigations into the mechanism of the postexposure protection by evaluating the role of humoral and cell-mediated immunity and interferon. Transcription and replication of rabies virus RNA in cultured cells and mouse brain will be studied with high specific radioactivity probes using inhibitors of virus replication including defective-interfering virus particles. Messenger RNA molecules will be sized and their relationships to the five structural proteins deduced. The comparative analysis of defective particle RNA will be extended and include oligo-nucleotide fingerprinting. We will continue to study the generation of defective interfering rabies virions in vivo and to assess the relative roles of DI virions, interferon and the immune response in determination of non-lethal, autointerfering, or fully lethal mouse death responses to different virus strains. The neuroblastoma cell model for studying rabies neuronal cell interactions will be further exploited, particularly in the areas of studying chronic virus infection and characterizing the replication of street viruses.